ABSTRACT
Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.
ABSTRACT
Diabetic nephropathy (DN) is a hyperglycemia-induced progressivedevelopment of renal insufficiency. Excessive glucose can increase mitochondrialreactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction.Our previous study indicated that cilostazol (CTZ) can reduce ROS levelsand decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes.This study investigated the potential mechanisms of CTZ in rats with DN and in highglucose-treated mesangial cells. Male Sprague–Dawley rats were fed 5 mg/kg/day ofCTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealedthat CTZ reduced the thickness of the glomerular basement membrane and improvedmitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatmentreduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemiaand interacted with the intrinsic pathway for regulating cell apoptosis as anantiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROSproduction, altered the apoptotic status, and down-regulated transforming growthfactor beta (TGF-) and nuclear factor kappa light chain enhancer of activated B cells(NF-B). Base on the results of our previous and current studies, CTZ decelerationof hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenanceof the mitochondrial function and reduction in TGF- and NF-B levels.
ABSTRACT
After bathing at a hot spring resort, a 75-year-old man presented to the emergency department because of seizure-like attack with loss of conscious. This is the first case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in Taiwan. PAM was diagnosed based on detection of actively motile trophozoites in cerebrospinal fluid using a wet-mount smear and the Liu's stain. The amoebae were further confirmed by PCR and gene sequencing. In spite of administering amphotericin B treatment, the patient died 25 days later.